A new, broad-spectrum azole antifungal: posaconazole ? mechanisms of action and resistance, spectrum of activity

The emergence or re-emergence of viruses with epidemic and/or pandemic potential, such as Ebola, Zika, Middle East Respiratory Syndrome (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 1 and 2 (SARS and SARS-CoV-2) viruses, or new strains of influenza represents significant human health threats due to the absence of available treatments. Vaccines represent a key answer to control these viruses. However, in the case of a public health emergency, vaccine development, safety, and partial efficacy concerns may hinder their prompt deployment. Thus, developing broad-spectrum antiviral molecules for a fast response is essential to face an outbreak crisis as well as for bioweapon countermeasures. So far, broad-spectrum antivirals include two main categories: the family of drugs targeting the host-cell machinery essential for virus infection and replication, and the family of drugs directly targeting viruses. Among the molecules directly targeting viruses, nucleoside analogues form an essential class of broad-spectrum antiviral drugs. In this review, we will discuss the interest for broad-spectrum antiviral strategies and their limitations, with an emphasis on virus-targeted, broad-spectrum, antiviral nucleoside analogues and their mechanisms of action.

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Prospective pharmacological effects of psoralen photoxidation products and their cycloadducts with aminothiols: chemoinformatic analysis

Bulletin of Russian State Medical University ◽

10.24075/brsmu.2020.059 ◽

2020 ◽

Author(s):

VV Skarga ◽

AD Zadorozhny ◽

BV Shilov ◽

EV Nevezhin ◽

VV Negrebetsky ◽

...

Keyword(s):

Broad Spectrum ◽

Mechanisms Of Action ◽

Therapeutic Use ◽

Therapeutic Effects ◽

Pharmacological Effects ◽

Puva Therapy ◽

New Directions

Psoralens are medicinal photosensitizing furocoumarins which are used in photochemotherapy and photoimmunotherapy of dermatoses. Psoralen photooxidation products may be involved in therapeutic effects, but the possible mechanisms of their action remain unclear. The study was aimed to assess the prospective pharmacological effects and mechanisms of activity for six previously identified ortho–hydroxyformyl-containing psoralen photooxidation products and their cycloadducts with aminothiols, as well as for structurally similar compounds (furocoumaric acid and tucaresol). Chemoinformatic analysis of the prospective pharmacological effects and mechanisms of action of these compounds was performed using the PASS and PharmaExpert software. The predicted pharmacological effects partially confirmed by previous studies highlight the possible involvement of psoralen photooxidation products in the effects of PUVA therapy or photopheresis during the course of dermatoses and proliferative disorders treatment. A broad spectrum of pharmacological effects found for furocoumaric acid and cycloadducts of coumarinic and benzofuranic photoproducts of psoralen with cysteine and homocysteine appoints new directions of research relating to therapeutic use of psoralens.

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Enhancement of Biocontrol Efficacy of Pichia kudriavzevii Induced by Ca Ascorbate against Botrytis cinerea in Cherry Tomato Fruit and the Possible Mechanisms of Action

Microbiology Spectrum ◽

10.1128/spectrum.01507-21 ◽

2021 ◽

Vol 9 (3) ◽

Author(s):

Keyu Sun ◽

Ziwuzhen Wang ◽

Xuanqing Zhang ◽

Ze Wei ◽

Xue Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Broad Spectrum ◽

Tomato Fruit ◽

Mechanisms Of Action ◽

Cherry Tomato ◽

Pichia Kudriavzevii ◽

Biocontrol Efficacy ◽

Broad Spectrum Resistance ◽

Fruit Decay ◽

Antagonistic Yeast

Antagonistic yeast is a promising way to control postharvest fruit decay because of its safety and broad-spectrum resistance. However, the biocontrol efficacy of yeast is limited by environmental stress, such as oxidative stress.

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Potential role of hypovitaminosis D and vitamin D supplementation during COVID-19 pandemic

QJM ◽

10.1093/qjmed/hcaa234 ◽

2020 ◽

Cited By ~ 1

Author(s):

M Verdoia ◽

G De Luca

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Broad Spectrum ◽

Potential Role ◽

Hypovitaminosis D ◽

Mechanisms Of Action ◽

Vitamin D Supplementation ◽

Current Status ◽

Special Focus

Summary Vitamin D deficiency is a pandemic disorder affecting over 1 billion of subjects worldwide and displaying a broad spectrum of implications on cardiovascular and inflammatory disorders. Since the initial reports of the association between hypovitaminosis D and COVID-19, Vitamin D has been pointed as a potentially interesting treatment for SARS-CoV-2 infection. We provide an overview on the current status of vitamin D deficiency, the mechanisms of action of vitamin D and the current literature on the topic, with a special focus on the potential implications for COVID-19 pandemic.

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Plant Defensins from a Structural Perspective

International Journal of Molecular Sciences ◽

10.3390/ijms21155307 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5307 ◽

Cited By ~ 1

Author(s):

Valentina Kovaleva ◽

Irina Bukhteeva ◽

Oleg Y. Kit ◽

Irina V. Nesmelova

Keyword(s):

Anticancer Activity ◽

Broad Spectrum ◽

Mammalian Cells ◽

Mechanisms Of Action ◽

Structure Dynamics ◽

Plant Defensins ◽

Structural Perspective

Plant defensins form a family of proteins with a broad spectrum of protective activities against fungi, bacteria, and insects. Furthermore, some plant defensins have revealed anticancer activity. In general, plant defensins are non-toxic to plant and mammalian cells, and interest in using them for biotechnological and medicinal purposes is growing. Recent studies provided significant insights into the mechanisms of action of plant defensins. In this review, we focus on structural and dynamics aspects and discuss structure-dynamics-function relations of plant defensins.

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Dithiolopyrrolones: biosynthesis, synthesis, and activity of a unique class of disulfide-containing antibiotics

Natural Product Reports ◽

10.1039/c3np70106a ◽

2014 ◽

Vol 31 (7) ◽

pp. 905-923 ◽

Cited By ~ 55

Author(s):

Bo Li ◽

Walter J. Wever ◽

Christopher T. Walsh ◽

Albert A. Bowers

Keyword(s):

Natural Products ◽

Broad Spectrum ◽

Mechanisms Of Action ◽

Anticancer Activities

Dithiolopyrrolone natural products have unique structures and exhibit a broad-spectrum of antimicrobial and anticancer activities. Isolated in the late 1940s, these molecules have attracted an increasing interest towards their biosynthesis, synthesis and mechanisms of action.

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Broad Spectrum Algae Compounds Against Viruses

Frontiers in Microbiology ◽

10.3389/fmicb.2021.809296 ◽

2022 ◽

Vol 12 ◽

Author(s):

Jacqueline Graff Reis ◽

Rafael Dorighello Cadamuro ◽

Ariadne Cristiane Cabral ◽

Izabella Thaís da Silva ◽

David Rodríguez-Lázaro ◽

...

Keyword(s):

Pharmaceutical Industry ◽

Bioactive Compounds ◽

Broad Spectrum ◽

Mechanisms Of Action ◽

Viral Control ◽

Control Applications ◽

Enveloped Viruses ◽

Food Industries ◽

Animal Medicine ◽

Algal Products

The pharmaceutical industry is currently trying to develop new bioactive compounds to inactivate both enveloped and non-enveloped viruses for therapeutic purposes. Consequently, microalgal and macroalgal bioactive compounds are being explored by pharmaceutical, as well as biotechnology and food industries. In this review, we show how compounds produced by algae include important candidates for viral control applications. We discuss their mechanisms of action and activity against enveloped and non-enveloped viruses, including those causing infections by enteric, parenteral, and respiratory routes. Indeed, algal products have potential in human and animal medicine.

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Non-neutralizing Antibodies Directed at Conservative Influenza Antigens

Acta Naturae ◽

10.32607/20758251-2019-11-4-22-32 ◽

2019 ◽

Vol 11 (4) ◽

pp. 22-32

Author(s):

E. S. Sedova ◽

D. N. Scherbinin ◽

A. A. Lysenko ◽

S. V. Alekseeva ◽

E. A. Artemova ◽

...

Keyword(s):

Influenza Virus ◽

Broad Spectrum ◽

Neutralizing Antibodies ◽

Matrix Protein ◽

Humoral Response ◽

Mechanisms Of Action ◽

Influenza Vaccines ◽

Complement Dependent Cytotoxicity ◽

The Moment ◽

New Vaccines

At the moment, developing new broad-spectrum influenza vaccines which would help avoid annual changes in a vaccines strain set is urgency. In addition, developing new vaccines based on highly conserved influenza virus proteins could allow us to better prepare for potential pandemics and significantly reduce the damage they cause. Evaluation of the humoral response to vaccine administration is a key aspect of the characterization of the effectiveness of influenza vaccines. In the development of new broad-spectrum influenza vaccines, it is important to study the mechanisms of action of various antibodies, including non-neutralizing ones, as well as to be in the possession of methods for quantifying these antibodies after immunization with new vaccines against influenza. In this review, we focused on the mechanisms of anti-influenza action of non-neutralizing antibodies, such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and antibody-mediated complement-dependent cytotoxicity (CDC). The influenza virus antigens that trigger these reactions are hemagglutinin (HA) and neuraminidase (NA), as well as highly conserved antigens, such as M2 (ion channel), M1 (matrix protein), and NP (nucleoprotein). In addition, the mechanisms of action and methods for detecting antibodies to neuraminidase (NA) and to the stem domain of hemagglutinin (HA) of the influenza virus are considered.

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